Dry eye syndrome (or ‘dry eye’), also called keratoconjunctivitis sicca, is an eye disease that affects millions of people each year. Particularly, this disease is known to be common in women after menopause due to hormonal changes caused by stopping menstruation. The degrees of dry eye syndrome are varied from person to person. Patients with mild symptoms may feel a burning sensation, dryness, and a foreign body sensation, while patients with severe symptoms may have seriously damaged vision. Other diseases such as Sjogren's syndrome and cicatricial pemphigoid, sometimes, also exhibit complex dry eye syndrome.
Based on research results until now, it has been understood that autoimmune response associated with cytokines, antigen-labeled cells, and the like, occur on the ocular surface due to various stress, which causes immune cells to agglomerate on the corneal tissue, resulting in damaging the tissue, and thus induces dry eye syndrome.
As representative treatments of dry eye syndrome, artificial tears are used to complement an ocular tear film or reduce the evaporation of tears to stabilize the tear film. In addition, a tear insert may be used to stimulate the production of tears. A main ingredient of the artificial tear is cellulose ether, carbomer, polyvinyl alcohol, polyvinyl pyrollidone, sodium hyaluronate, or the like, and the artificial tear is prepared by dissolving it in buffer or isotonic saline. These ingredients make the solution viscous to thereby prevent the solution from easily flowing from the eye, prevent the evaporation of tear, and serve as a lubricant. However, these treatments have a limitation in that they are not fundamental treatments but symptomatic treatments.
Meanwhile, as it was discovered that the causes of dry eye are associated with inflammation response on the ocular surface, researches and efforts to apply various kinds of anti-inflammatory materials for treatment were carried out and their effects were proven.
Specifically, it has been reported that ocular tissue such as the lachrymal gland and meibomian gland of patients suffering from dry eye syndromes exhibited unbalanced and excessive inflammation, and it has been known that various compounds, for example, steroids, cytokine secretion inhibitors, cyclosporine A, and 15-HETE, are effective for alleviating the dry eye syndrome.
Tumor necrosis factor alpha (TNFα) is an important factor associated with the inflammation response, and bind to human TNF receptor (TNFR) I or II to thereby induce various cell responses including apoptosis and inflammation response. After it was proven that various autoimmune-related inflammatory diseases can be treated by inhibiting the binding of TNFα and TNFR, various TNFα inhibitors have been developed. Representative examples of TNFα inhibitors may be Etanercept (product name: Enbrel) made from the combination of soluble TNFRII with an FC portion, Infliximab (product name: Remicade) and Adalimumab (product name: Humira), which are antibodies against TNFα, and the like. These are mainly used as treatments for rheumatoid arthritis, psoriasis, Crohn's disease, and the like.
Meanwhile, it has been disclosed that TNFα inhibitors have treatment effects for dry eye (U.S. Pat. No. 6,428,787B, U.S. Pat. No. 6,379,666B, U.S. Pat. No. 6,177,077B, U.S. Pat. No. 6,204,270B, US 2004/0126372A, WO 00/27421A). In addition, US 2009/0098136A discloses that Etanercept and Infliximab have effects in treating the dry eye syndrome in animal models and administration of the two materials in the form of eye drop tends to improve tear breakup time and corneal staining.
However, the demand is still urgent for new treatments for dry eye syndrome showing higher therapeutic efficacy, particularly, new treatments for dry eye syndrome containing a TNFα inhibitor as an effective ingredient.